SYNTHESIS OF CONGENERS OF ADENOSINE RESISTANT TO DEAMINATION BY ADENOSINE-DEAMINASE
SYNTHESIS OF CONGENERS OF ADENOSINE RESISTANT TO DEAMINATION BY ADENOSINE-DEAMINASE
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DOI：
10.1039/c39890000878
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发表时间：
1989-07-01
影响因子：
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通讯作者：
SELLS, TB
中科院分区：
文献类型：
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作者：
NAIR, V;PURDY, DF;SELLS, TB
开发有效的和区域特异性的腺嘌呤环功能化方法对于设计和合成这一家族具有治疗作用的核苷是至关重要的。特别令人感兴趣的是战略性官能化，其结果是产生完全抵抗普遍存在的哺乳动物酶腺苷脱氨酶(ADA)的水解性脱氨的同系物。这种酶限制了腺苷类似物的治疗效果，包括那些显示出显著抑制人类免疫缺陷病毒(HIV-1)的细胞病变效应的2‘，3’-二脱氧腺苷(DDA)。我们报道了新的，金属介导的一些腺苷类似物的合成，这些核苷对哺乳动物的腺苷脱氨酶的行为。
Development of methodologies for the efficient and regiospecific functionalization of the adenine ring is of fundamental importance in the design and synthesis of therapeutically useful nucleosides of this family. Of particular interest are strategic functionalizations that result in congeners that are totally resistant to hydrolytic deamination by the ubiquitous mammalian enzyme adenosine deaminase (ADA). This enzyme limits the therapeutic efficacy of adenosine analogues, including those such as 2', 3'-dideoxyadenosine (ddA) which exhibit significant inhibition of the cytopathic effect of the human immunodeficiency virus (HIV-1). We report on the novel, metal-mediated syntheses of some analogues of adenosine specifically functionalized at the 2-position and the behaviour of these nucleosides towards mammalian adenosine deaminase.